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A former NFL veteran who played for the New York Giants along with the Minnesota Vikings, Matt Mitrione gained recognition in MMA when he competed on the tenth season of The Ultimate Fighter reality show. More than his athletic ability or technical proficiency, Mitrione was known for his violent outbursts and temper tantrums, earning him the nickname “Meathead” from coach Rashad Evans. Although Mitrione did not win the TUF tournament, he won his first two fights in the UFC by knockout, defeating Marcus Jones and Kimbo Slice after the show and sending Slice out of the UFC.

He followed those two wins with a Fight of the Night decision victory over Joey Beltran. Mitrione then went on to TKO Tim Hague in the first round and Christian Morecraft in the second round. Mitrione would then taste defeat for the first time in the UFC losing a Unanimous Decision to Cheick Kongo. He was scheduled to fight Rob Broughton but the bout was cancelled two separate times. He was then scheduled to face Phil De Fries at UFC 155 but was moved up to the TUF 16 Finale against fellow TUF season 10 competitor and eventual winner, Roy Nelson. Mitrione was tapped to replace the other coach from the show, Shane Carwin, after he was injured. Mitrione lost to Nelson, via TKO, at 2:58 of the first round.

Mitrione would get back on the winning track when he defeated Phil De Fries by TKO in 19 seconds at UFC on Fuel TV 9. However following the fight during an interview Mitrione had strong words and opinions about transgender fighter Fallon Fox which led to the UFC suspending his contract due to breaking the UFC's code of conduct. The UFC was quick to forgive Mitrione for his words however, got a fight against fellow TUF 10 alumni Brendan Schaub at UFC 165 in which he would be submitted in the first round.

He would get back in the win column however with a first round TKO over Shawn Jordan in a performance of the night bonus. He would get a second straight TKO finish when he took out Derrick Lewis in the first round.

Riding a two-fight win streak, Mitrione would be slated to face longtime UFC heavyweight staple, Gabriel Gonzaga. Their contest would be set at UFC on Fox 13. Mitrione would go on to win via KO in the first round bringing his win streak to three.

Riding a three fight win streak, Mitrione looked to make it 4 in a row when he faced Ben Rothwell, UFC Fight Night 68: Boetsch vs. Henderson. In Mitrione fashion, he came out aggressively, trying to take over the pace of the fight. Early in Round 1 he shot for a takedown, which was stuffed by Rothwell. Rothwell took the opportunity to sink in a guillotine choke, forcing Mitrione to quickly tap at 1:54 in Round 1.